Synthesis of high density macromolecular arrays is known. Such high density macromolecular arrays include nucleic acid arrays, peptide arrays, and carbohydrate arrays. See, for example, the U.S. Pat. Nos. 5,143,854, 5,384,261, 5,405,783, and 5,424,186.
One method of preparing macromolecular arrays involves photolithographic techniques using photocleavable protecting groups. Briefly, the method includes attaching photoremovable groups to the surface of a substrate, exposing selected regions of the substrate to light to activate those regions, attaching a monomer with a photoremovable group to the activated regions, and repeating the steps of activation and attachment until macromolecules of the desired length and sequence are synthesized. See U.S. Pat. Nos. 5,324,663, 5,384,261, 5,405,783, and 5,412,087.
Additional methods and techniques applicable to array synthesis have been described in the U.S. Pat. Nos. 5,424,186, 5,445,934, 5,451,683, 5,482,867, 5,489,678, 5,491,074, 5,510,270, 5,527,681, 5,550,215, 5,571,639, 5,593,839, 5,599,695, 5,624,711, 5,631,734, 5,677,195, 5,744,101, 5,744,305, 5,753,788, 5,770,456, 5,831,070, and 5,856,011.
Traditional substrates used in array synthesis consist of flat two-dimensional surfaces or three-dimensional surfaces such as a porous matrix or a cross-linked polymer gel. While these substrates have been satisfactory in general, as the density of the array increased, signal to noise ratio under assay conditions decreased due to crowding, resulting often in decreased performance. This crowding and performance issues become more important as more applications for high density macromolecular arrays are being developed. Thus, there is a need for high density macromolecular arrays with good or improved performance under assay conditions. The present invention meets this need.